Paeonol suppresses lipid accumulation in macrophages via upregulation of the ATP‑binding cassette transporter A1 and downregulation of the cluster of differentiation 36

  • Authors:
    • Xiuying Li
    • Yuanda Zhou
    • Chao Yu
    • Hui Yang
    • Chengzhi Zhang
    • Yun Ye
    • Shunlin Xiao
  • View Affiliations

  • Published online on: November 17, 2014     https://doi.org/10.3892/ijo.2014.2757
  • Pages: 764-774
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Abstract

Paeonol, a potent antioxidant isolated from cortex moutan, possesses athero‑protective activity, yet the detailed mechanisms are not fully investigated. This study was conducted to explore the role of paeonol and its underlying mechanisms in RAW264.7 macrophages and apolipoprotein E‑deficient (ApoE‑/‑) mice. Paeonol treatment significantly attenuated intracellular lipid accumulation in macrophages, which may be the result of decreased oxidized low‑density lipopro­tein (ox‑LDL) uptake and increased cholesterol efflux. Additionally, paeonol markedly inhibited the mRNA and protein expression of the cluster of differentiation 36 (CD36) by decreasing nuclear translocation of c‑Jun [a subunit of activator protein‑1 (AP‑1)]. Moreover, paeonol upregulated the protein stability of ATP‑binding cassette transporter A1 (ABCA1) by inhibiting calpain activity, while ABCA1 mRNA expression was not altered. Furthermore, small hairpin RNA (shRNA) targeting haem oxygenase‑1 (HO‑1) inhibited the paeonol‑mediated beneficial effects on the expression of c‑Jun, CD36, ABCA1, calpain activity and lipid accumulation in macrophages. Accordingly, paeonol retarded the progress of atherosclerosis in ApoE‑/‑ mice and modulated the expression of CD36 and ABCA1 in aortas similarly to that observed in macrophages. These results indicate that paeonol provides protective effects on foam cell formation by a novel HO‑1‑dependent mediation of cholesterol efflux and lipid accumulation in macrophages.
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February-2015
Volume 46 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Li X, Zhou Y, Yu C, Yang H, Zhang C, Ye Y and Xiao S: Paeonol suppresses lipid accumulation in macrophages via upregulation of the ATP‑binding cassette transporter A1 and downregulation of the cluster of differentiation 36. Int J Oncol 46: 764-774, 2015.
APA
Li, X., Zhou, Y., Yu, C., Yang, H., Zhang, C., Ye, Y., & Xiao, S. (2015). Paeonol suppresses lipid accumulation in macrophages via upregulation of the ATP‑binding cassette transporter A1 and downregulation of the cluster of differentiation 36. International Journal of Oncology, 46, 764-774. https://doi.org/10.3892/ijo.2014.2757
MLA
Li, X., Zhou, Y., Yu, C., Yang, H., Zhang, C., Ye, Y., Xiao, S."Paeonol suppresses lipid accumulation in macrophages via upregulation of the ATP‑binding cassette transporter A1 and downregulation of the cluster of differentiation 36". International Journal of Oncology 46.2 (2015): 764-774.
Chicago
Li, X., Zhou, Y., Yu, C., Yang, H., Zhang, C., Ye, Y., Xiao, S."Paeonol suppresses lipid accumulation in macrophages via upregulation of the ATP‑binding cassette transporter A1 and downregulation of the cluster of differentiation 36". International Journal of Oncology 46, no. 2 (2015): 764-774. https://doi.org/10.3892/ijo.2014.2757